Methods:

SNPs were genotyped using TaqMan or pyrosequencing. RANKL expression levels in plasma, PBMC and isolated T cells were quantified using ELISA and RT-PCR. In vitro site-directed mutagenesis of rs7984870 within the 2kb RANKL promoter was performed to drive the luciferase reporter gene in transfected cells.

Conclusion:

Association of CC genotype of rs7984870 with younger RA onset has been replicated in several independent cohorts, and confers an elevated promoter activity after stimulation. Elevated inducible RANKL mRNA and protein levels may predispose to earlier development of seropositive (RF+ or anti-CCP+) RA in EA and AA patients.